Method for preparing pharmaceutical compositions intended for oral administration comprising one or more active ingredients and the compositions comprising same

Abstract

The present invention relates to fexofenadine granules, to a composition containing them and to a process for the hot-melt coating of fexofenadine. The process for the hot-melt coating of fexofenadine allows efficient masking of its bitter taste without, however, unacceptably slowing down its dissolution.

1 - 26 . (canceled) 
     
     
         27 . A fexofenadine composition comprising (a) a granule centre formed from active principle grains aggregated in the presence of a binder and optionally of a lubricant or preferably of a diluent, and (b) a layer for coating the said granule centre formed from a fatty matrix, in which composition whereby
 the fexofenadine represents at least 10%, preferably 15% or even 20% by weight relative to the weight of the composition; the active principle represents not more than 90%, preferably not more than 60% or 50% by weight relative to the weight of the composition, or even less than 40% by weight relative to the weight of the composition, preferably the active principle represents from 20% to 40% relative to the weight of the composition;   the fatty matrix represents more than 10% by weight, preferably from 50% to 85% by weight of the composition, the fatty matrix optionally comprising an adjuvant, preferably chosen from hydrophilic agents, surfactants or mixtures thereof, and these adjuvants representing less than 10% by weight of the composition and preferably from 1% to 3% by weight relative to the weight of the composition;   the binder, preferably a hydrophilic agent chosen from hydrophilic polymers and hot-melt agents, represents from 0.2% to 18% by weight relative to the weight of the composition, preferably the binder represents less than 18% by weight for a hot-melt agent, or even, preferably, the binder represents less than 10% by weight for a hydrophilic polymer relative to the weight of the composition;   the diluent, if necessary, as filler represents a content of from 0 to 78.8%, preferably from 0 to 39% and preferably from 5% to 15% by weight relative to the weight of the composition;   the lubricant, if necessary, as flow agent represents a content of from 0 to 1.8% relative to the weight of the composition.   
     
     
         28 . A fexofenadine composition according to  claim 27 , in which the said fatty matrix is formed from C14 to C22 and preferably C16 to C18 long-carbon-chain saturated fatty acids, pure or as mixtures, and/or the corresponding fatty alcohols thereof, and the binder is chosen from hydrophilic polymers. 
     
     
         29 . A fexofenadine composition according to  claim 28 , in which the said fatty matrix is formed from stearic acid. 
     
     
         30 . A fexofenadine composition according to  claim 27 , in which the said fatty matrix comprises an adjuvant chosen from the group of surfactants (phospholipid, polysorbate, lauryl sulfate), hydrophilic excipients such as sucrose, polyols, cellulose, lactose, silica, dicalcium phosphate, carbonates, starch, macrogols, agents that are soluble at acidic pH (methacrylic derivatives), pure or as mixtures, preferably phospholipids. 
     
     
         31 . A fexofenadine composition according to  claim 30 , in which the adjuvant is soya lecithin. 
     
     
         32 . A fexofenadine composition according to  claim 27 , in which the adjuvant is a surfactant that represents less than 10% by weight, preferably less than 5% by weight, preferably from 1% to 3%, or even from 1% to 2%, by weight relative to the weight of the composition. 
     
     
         33 . A fexofenadine composition according to  claim 27 , in which the binder is povidone and the diluent is corn starch. 
     
     
         34 . A fexofenadine composition according to  claim 27 , in which the amount of fexofenadine represents more than 10% by weight and ranges up to 90% by weight relative to the weight of the composition. 
     
     
         35 . A fexofenadine composition according to  claim 27 , in which the amount of fexofenadine represents more than 10% by weight of the composition and the fatty matrix comprises an adjuvant. 
     
     
         36 . A process for preparing a fexofenadine composition as defined according to  claim 27 , the said process comprising the steps of:
 E1) preparing the granule centre by spraying an aqueous solution, an organic solution or a mixture thereof comprising a binder or by spraying a molten binder onto the fexofenadine alone or as a mixture with a lubricant and/or preferably a diluent;   E2) coating by spraying onto the granules a fatty matrix melted beforehand in a melting vessel at a temperature from about 10 to 20° C. above its melting point;   E3) cooling of the composition obtained.   
     
     
         37 . A process for preparing a composition according to  claim 36 , in which:
 the fexofenadine represents at least 10% and not more than 90%, preferably from 20% to 50%, and   the fatty matrix comprising an adjuvant represents more than 10% by weight, preferably 50% and up to 85% by weight of the composition.   
     
     
         38 . A process for preparing a composition according to  claim 36 , in which:
 the fexofenadine represents less than 40% by weight, preferably from 20% to 40% and advantageously from 30% to 40% relative to the weight of the composition, and   the fatty matrix represents more than 10% by weight, preferably 50% and up to 85% by weight of the composition, advantageously from 50% to 60% by weight of the composition.   
     
     
         39 . A process according to  claim 36 , in which the size of the coated granules obtained after step E3) is less than 500 μm, preferably less than 350 μm, preferably ranging from 50 to 350 μm. 
     
     
         40 . A process according to  claim 36 , in which the particle size of the final product obtained at step E3) is distributed according to the following range:
 less than 15% by weight of the coated granules are greater than 500 μm;   more than 80% by weight, preferably more than 90% by weight, of the coated granules are between 350 and 50 μm, and;   less than 20% by weight, preferably less than 5% by weight, of the coated granules are less than 50 μm.   
     
     
         41 . A process according to  claim 36 , in which the aqueous or organic solution used in step E1 comprises, as binder, a hydrophilic polymer, preferably chosen from the group of cellulose derivatives (hydroxypropylcellulose or ethylcellulose), povidone (polyvinylpyrrolidone), sucrose, gums, starches, gelatin, macrogols (polyethylene glycols), which represent approximately from 15% to 45% and preferably 20% to 40% by weight of the said solution. 
     
     
         42 . A process according to  claim 36 , in which the aqueous or organic solution used in step E1 sprayed onto the fexofenadine is mixed with corn starch. 
     
     
         43 . A process according to  claim 36 , in which the weight percentage of the binder constituting the coating of the granule obtained in step E1 represents from 1% to 7% by weight relative to the weight of the composition for a hydrophilic polymer. 
     
     
         44 . A process according to  claim 36 , followed by a step E4 of formulation of the coated granules obtained in step E3 with excipients such as diluents, fillers, viscosity modifiers, disintegrants, dyes, sweeteners, salivating agents, flavourings, preserving agents, wetting agents, effervescent agents, lubricants, buffers and sequestrants for the manufacture of an oral formulation in the form of a composition of granules to be swallowed for sachets, granules for a drinkable suspension, granules for tablets or granules for orodispersible tablets. 
     
     
         45 . A fexofenadine composition that may be obtained according to the process described in  claim 36 . 
     
     
         46 . A pharmaceutical composition comprising the fexofenadine composition as described in one of  claims 27 . 
     
     
         47 . A composition according to  claim 46 , characterized in that it is in the form of a sachet comprising a composition of granules to be swallowed or a sachet for a drinkable suspension and characterized in that it contains one or more excipients, preferably chosen from diluents, viscosity modifiers, sequestrants, buffers, preserving agents, lubricants, wetting agents, effervescent agents, dyes, sweeteners, salivating agents and flavourings, and mixtures thereof. 
     
     
         48 . A composition according to  claim 46 , characterized in that it is in the form of tablets, to be chewed, swallowed or sucked, or orodispersible tablets with masked taste, and characterized in that it contains one or more excipients, preferably chosen from diluents, binders, lubricants, salivating agents, anaesthetics, wetting agents, preserving agents, disintegrants, dyes, sweeteners, flavourings, and mixtures thereof. 
     
     
         49 . A sachet or tablet according to  claim 47 , characterized in that the weight ratio of the fexofenadine composition as defined according to one of claim  1  relative to the weight amount of excipient in the sachet or tablet ranges from 0.2 to 0.8. 
     
     
         50 . A method of using a fexofenadine composition as defined in  claim 27  for the preparation of a pharmaceutical composition that is in the form of sachets comprising a composition of granules to be swallowed or for a drinkable suspension, tablets to be chewed, tablets to be swallowed, tablets to be sucked, or orodispersible tablets with masked taste. 
     
     
         51 . A pharmaceutical composition comprising the fexofenadine composition of  claim 27  as prepared according to the process as described in  claim 36 .